Featured Research

from universities, journals, and other organizations

New Computational Model Allows For Better Understanding Of AIDS Drug

Date:
July 25, 2006
Source:
Virginia Tech
Summary:
Researchers at the Virginia Bioinformatics Institute (VBI) at Virginia Tech have developed a computational model that allows scientists to better understand the metabolism and toxicity of the HIV/AIDS drug zidovudine (azidothymidine, AZT).

Researchers at the Virginia Bioinformatics Institute at Virginia Tech have developed a computational model that allows scientists to better understand the metabolism and toxicity of the HIV/AIDS drug zidovudine (azidothymidine, AZT).

AZT is used successfully as part of Highly Active Anti-Retroviral Therapy (HAART) to control the level of the human immunodeficiency virus in HIV-infected individuals. However, long-term use of AZT may lead to side-effects in some patients. David Samuels and coworkers are interested in finding out whether the toxic side effects of AZT can eventually be minimized or even eliminated. For this purpose, they have been developing a detailed computational model that allows scientists to simulate the biochemical reactions that take place when AZT is metabolized in cells, including their mitochondria, under different metabolic conditions. Drugs like AZT may interfere with DNA replication in the mitochondria, the energy factories of our cells, and can lead to potentially fatal side effects in patients undergoing HAART treatment.

“HAART is one of the biggest success stories in modern medicine. The goal of our work is to help improve this successful treatment by understanding the toxic effects that AZT can have in some people. There are many different ways that AZT could possibly interfere with mitochondria to cause the toxic side-effects. Our job is to model these proposed toxicity mechanisms to see which ones could actually lead to the mitochondrial defects found in AIDS patients, ”said Dr Samuels, assistant professor at Virginia Bioinformatics Institute. “It is possible that no single mechanism is responsible for the toxicity, but that instead a combination of multiple effects is needed. That is the kind of problem that needs a systems biology approach.”

When AZT reaches a cell, it is subject to some of the same metabolic modifications or phosphorylation events that are encountered by the four naturally occurring deoxynucleosides, the building blocks used to make DNA. However, modified AZT molecules lack a specific chemical group (a hydroxyl group) that would allow DNA replication to continue. This results in premature termination of DNA synthesis. It is thought that the triphosphorylated form of AZT can enter the mitochondrial matrix, the inner core of the mitochondrion, and disrupt the replication of mitochondrial DNA by prematurely terminating DNA synthesis.

“We’re just starting our work. It is too early to say what the mechanism of mitochondrial toxicity of AZT is. The inhibition of deoxynucleoside metabolism is one possibility. The incorporation of AZT into mitochondrial DNA is another,” added Samuels. “The detailed computational model that we have developed should allow researchers to explore different hypotheses as to why AZT can lead to such debilitating side effects in some patients undergoing anti-retroviral treatment.”

This research is supported by National Institutes of Health grant DK070533.

The Virginia Bioinformatics Institute (VBI) at Virginia Tech has a research platform centered on understanding the “disease triangle” of host–pathogen–environment interactions in plants, humans and other animals. By successfully channeling innovation into transdisciplinary approaches that combine information technology and biology, researchers at VBI are addressing some of today’s key challenges in the biomedical, environmental and plant sciences.


Story Source:

The above story is based on materials provided by Virginia Tech. Note: Materials may be edited for content and length.


Cite This Page:

Virginia Tech. "New Computational Model Allows For Better Understanding Of AIDS Drug." ScienceDaily. ScienceDaily, 25 July 2006. <www.sciencedaily.com/releases/2006/07/060725074310.htm>.
Virginia Tech. (2006, July 25). New Computational Model Allows For Better Understanding Of AIDS Drug. ScienceDaily. Retrieved April 24, 2014 from www.sciencedaily.com/releases/2006/07/060725074310.htm
Virginia Tech. "New Computational Model Allows For Better Understanding Of AIDS Drug." ScienceDaily. www.sciencedaily.com/releases/2006/07/060725074310.htm (accessed April 24, 2014).

Share This



More Computers & Math News

Thursday, April 24, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Monkeys Are Better At Math Than We Thought, Study Shows

Monkeys Are Better At Math Than We Thought, Study Shows

Newsy (Apr. 23, 2014) A Harvard University study suggests monkeys can use symbols to perform basic math calculations. Video provided by Newsy
Powered by NewsLook.com
High Court to Hear Dispute of TV Over Internet

High Court to Hear Dispute of TV Over Internet

AP (Apr. 22, 2014) The future of Aereo, an online service that provides over-the-air TV channels, hinges on a battle with broadcasters that goes before the U.S. Supreme Court on Tuesday. (April 22) Video provided by AP
Powered by NewsLook.com
Aereo Takes on Broadcast TV Titans in Supreme Court Today

Aereo Takes on Broadcast TV Titans in Supreme Court Today

TheStreet (Apr. 22, 2014) Aereo heads to the Supreme Court today to fight for its right to stream broadcast TV over the Internet -- against broadcasters who say the start-up infringes upon copyright law. TheStreet Deputy Managing Editor Leon Lazaroff explains the importance of the case in the TV industry and details what the outcome of it could mean for broadcasters and for cloud storage services -- as Aereo allows its subscribers to not just watch live TV shows but also store content to a DVR in the cloud. Video provided by TheStreet
Powered by NewsLook.com
Lytro Introduces 'Illum,' A Professional Light-Field Camera

Lytro Introduces 'Illum,' A Professional Light-Field Camera

Newsy (Apr. 22, 2014) The light-field photography engineers at Lytro unveiled their next innovation: a professional DSLR-like camera called "Illum." Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins